Commercial opportunities exist in the cardiovascular drug, gene therapy, and device markets for a high-fidelity, predictive in vitro vascular model that can bridge the gap between high throughput screening and pre=clinical trials for cardiovascular drug discovery and gene therapy development. The goal of this proposal is to develop and validate design parameters for a unique vascular perfusion system to sustain intact vascular tissues for high fidelity in vitro modeling and testing. The system will provide an organ culture platform on which excised vascular tissue can be maintained under controlled in vitro conditions of shear stress and pulsatile pressure to generate results more predictive of in vivo responses. The Phase I study will be directed at designing a novel perfusion manifold system that allows for varied vessel sizes, is optimized for control and monitoring of desired flow (shear stress), pulse wave, and pH. Phase II will encompass optimization of system components including a variable pulse wave perfusion system and unitized nutrient and oxygenation flowpath with integral injection and non- invasive sampling. Appropriate sensor and feedback controls will be established to allow reproducibility, documentation, and quality assurance. PROPOSED COMMERCIAL APPLICATION: The vascular organ culture system will be commercialized for use as an in vitro tool for pre-clinical cardiovascular drug and gene therapy development as well as basic research. Example target applications include: cellular and molecular dysfunction in atherosclerosis, gene therapy vector development, and cardiovascular drug discovery.